Dilated cisternae of the ER resembling Russell Bodies (RBs) are induced in light (L) chain producing myeloma cell lines by transfection of a μ heavy (H) chain gene lacking the first constant domain (μΔCH1). RBs do not appear to be tissue specific, since they are also induced in a rat glioma cell line transfected with μΔCH1 and L chain genes. Efficient RB biogenesis requires H-L assembly and polymerization. The mutant Ig is partially degraded in a pre-Golgi compartment. The remnant, however, becomes an insoluble lattice when intersubunit disulphide bonds are formed. The resulting insoluble aggregate accumulates in RBs. Replacing the COOH-terminal cysteine of μΔCH1 chains with alanine reverses the RB-phenotype: the double mutant μ(ala)ΔCH1 chains assemble noncovalently with L and are secreted as H2L2 complexes. Similarly, secretion of μΔCH1 chains can be induced by culturing transfectant cells in the presence of reducing agents. The presence of RBs does not alter transport of other secretory or membrane molecules, nor does it affect cell division. Resident proteins of the ER and other secretory proteins are not concentrated in RBs, implying sorting at the ER level. Sorting could be the result of the specific molecular structure of the insoluble lattice. We propose that RBs represent a general response of the cell to the accumulation of abundant, nondegradable protein(s) that fail to exit from the ER.
|Number of pages||12|
|Journal||Journal of Cell Biology|
|Publication status||Published - 1991|
ASJC Scopus subject areas
- Cell Biology